Zinc attenuates tnf-mediated activation of NF-KB in endothelial cells

Endothelial cell dysfunction which contributes to atherosclerosis may be associated with activation of oxidative stress sensitive transcription factors such as nuclear factor kappa B (NF-KB), enhanced cytokine production and activity and alterations in adhesive properties of the endothelial surface. Zinc, a critical element in the maintenance of normal endothelial integrity, may protect against oxidative stress mediated by inflammatory cytokines. To investigate this hypothesis, endothelial cells were exposed to zinc-deficient media with or without zinc supplementation and then challenged with TNF. Subsequently, nuclear extracts were analyzed for NF-KB binding. Zinc supplementation resulted in a 90% increase in cellular zinc content. Cells cultured in zinc-deficient media expressed significant NF-KB binding which was not demonstrated in zincsupplemented cultures. It was also shown that a 1.5 h exposure to TNF (100 U/mL medium) significantly upregulated NF-KB expression, which was prevented by prior supplementation with physiological levels of zinc. These data suggest that zinc may block the inflammatory cytokine-mediated activation of oxidative stress sensitive transcription factors. Thus, zinc may have antiatherogenic properties by protecting the integrity of the vascular endothelium against oxidative stress and inflammatory insult.